A Reinterpretation of the Relationship Between Persistent and Resurgent Sodium Currents.

The resurgent sodium current (I NaR ) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, I NaR is thought to drive high rates of repetitive neuronal firing. However, I NaR is often studied in combination with the persistent or non-inactivating portion of sodium currents (I NaP ). We used dynamic clamp to test how I NaR and I NaP individually affect repetitive firing in adult cerebellar Purkinje neurons from male and female mice. We learned I NaR does not scale repetitive firing rates due to its rapid decay at subthreshold voltages, and that subthreshold I NaP is critical in regulating neuronal firing rate. Adjustments to the Nav conductance model used in these studies revealed I NaP and I NaR can be inversely scaled by adjusting occupancy in the slow inactivated kinetic state. Together with additional dynamic clamp experiments, these data suggest the regulation of sodium channel slow inactivation can fine-tune I NaP and Purkinje neuron repetitive firing rates.